Importance
Since bilateral simultaneous postoperative endophthalmitis (BSPOE) after immediate sequential bilateral cataract surgery (ISBCS) can be devastating for the patient, evaluating such cases ...in depth is important to maintaining patient safety.
Objective
To evaluate whether a systemic breach of sterility was associated with an outbreak of BSPOE after ISBCSs performed on the same day at a single community-based eye clinic.
Design, Setting, and Participants
This retrospective case series included all patients diagnosed with BSPOE at ophthalmology departments in Denmark following an infectious outbreak after ISBCSs performed at a single community-based eye clinic in December 2022.
Exposure
Bilateral simultaneous postoperative endophthalmitis acquired after ISBCS.
Main Outcome and Measures
Patient recovery from BSPOE after ISBCS was evaluated based on clinical and microbiological reports.
Results
A woman aged 71 years, a man aged 84 years, and a woman aged 79 years consecutively presented with symptoms of endophthalmitis at regional eye departments 4 to 8 days after ISBCS performed on the same date at the same eye clinic. Five of 6 infected eyes underwent vitrectomy, and all eyes received an intravitreous injection of antibiotics. The same strain of
Staphylococcus epidermidis
was isolated in 4 of 5 eyes that underwent vitrectomy. Contamination of viscoelastics was ruled out with repeated cultures. One eye was eviscerated due to phthisis. In another patient, the final visual acuity of the eye most severely affected was 20/63 Snellen equivalents. Visual acuity of the remaining eyes recovered to 20/25 (3 eyes in 2 patients) and 20/20 (1 eye) Snellen equivalents.
Conclusions and Relevance
The finding of the same strain of
S epidermidis
in all patient cultures suggests a systemic breach of sterility at the clinic on the day of ISBCS. The outcome of these cases emphasizes the need to adhere to a strict surgical methodology and sterile principles during ISBCS.
The time evolution of a quantum wave packet in the linear gravity potential is known as Quantum Bouncing Ball. The qBounce collaboration recently observed such a system by dropping wave packets of ...ultracold neutrons by a height of roughly 30 microns. In this article, space and momentum spectra as well as Wigner functions of the neutron wave functions in the gravitational field of the Earth are analyzed. We investigate the quantum states in the “preparation region”, into which they transition after exiting a narrow double-mirror system and where we would expect to observe free fall and bounces in classical physics. For this, we start from the stationary solutions and eigenvalues of the Schrödinger equation in terms of Airy functions and their zeros. Subsequently, we examine space and momentum distributions as well as Wigner functions in phase space for pure and mixed quantum states. The possible influence of Yukawa-like forces for small distances of several micrometers from the mirror is included through first order perturbation calculations. Those allow us to study the resulting modifications of space and momentum distributions, and phase space functions.
Introduction
Concerns related to pain from intravitreal injections are one of the key factors mentioned by patients when asked about therapy. In this systematic review and network meta-analysis, we ...evaluate the literature of comparative clinical trials on the relationship between needle gauge size and pain experience during intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy.
Methods
We searched 12 literature databases on 14 October 2023 for comparative studies of gauge sizes for intravitreal anti-VEGF injections. The primary outcome of interest was the reported pain experience immediately after the injection. All outcomes of pain were transformed into standardized effect sizes using Cohen’s
d
. Using a network meta-analysis approach, we were able to compare all gauge sizes and rank them according to the reported pain experience.
Results
We identified nine eligible studies with data on a total of 998 patients and 1004 eyes. Needle sizes studied were 26-gauge, 27-gauge, 29-gauge, 30-gauge, 32-gauge, 33-gauge, and 34-gauge. A complete network was present, which allowed for a network meta-analysis. We used the thickest (26-gauge) needle as the reference group and observed a clear trend of lower pain experience with thinner gauge sizes (
d
: −0.4,
d
: −2.7,
d
: −3.8,
d
: −4.8,
d
: −4.5, and
d
: −5.3; respectively, for 27-gauge, 29-gauge, 30-gauge, 32-gauge, 33-gauge, and 34-gauge).
Conclusion
A gauge size of 30 or thinner may minimize patient discomfort related to intravitreal anti-VEGF therapy.
In article number 2001955, André R. Studart, Andres F. Arrieta, and co‐workers demonstrate a family of mechanical metamaterials exploiting sheets patterned with locally bistable domes. The ...metamaterial's strong hierarchical response enables tunable mechanical properties and programmed geometry adaptation. The strain energy stored by local dome inversion simplifies soft robotics grippers' actuation and enables memory and computation of spatially‐distributed mechanical signals in thin skins.
Spinocerebellar ataxia type 3 (SCA3)/Machado-Joseph disease (MJD) is a heritable proteinopathy disorder, whose causative gene, ATXN3, undergoes alternative splicing. Ataxin-3 protein isoforms differ ...in their toxicity, suggesting that certain ATXN3 splice variants may be crucial in driving the selective toxicity in SCA3. Using RNA-seq datasets we identified and determined the abundance of annotated ATXN3 transcripts in blood (n = 60) and cerebellum (n = 12) of SCA3 subjects and controls. The reference transcript (ATXN3–251), translating into an ataxin-3 isoform harbouring three ubiquitin-interacting motifs (UIMs), showed the highest abundance in blood, while the most abundant transcript in the cerebellum (ATXN3–208) was of unclear function. Noteworthy, two of the four transcripts that encode full-length ataxin-3 isoforms but differ in the C-terminus were strongly related with tissue expression specificity: ATXN3–251 (3UIM) was expressed in blood 50-fold more than in the cerebellum, whereas ATXN3–214 (2UIM) was expressed in the cerebellum 20-fold more than in the blood. These findings shed light on ATXN3 alternative splicing, aiding in the comprehension of SCA3 pathogenesis and providing guidance in the design of future ATXN3 mRNA-lowering therapies.
•Splice variants of ATXN3, the MJD/SCA3 causative gene, were analyzed in blood and cerebellum samples by RNA-seq.•ATXN3 transcripts diversity and abundance is higher in the cerebellum than in the blood.•The most abundant ATXN3 transcript in the cerebellum is noncoding and of unknown function.•The most abundant ATXN3 transcript in blood is the protein-coding canonical transcript.•2UIM-encoding transcripts are preferentially abundant in the cerebellum, while 3UIM transcripts are frequent in the blood.
Neuroblastoma is the most common extracranial solid tumour in children. Relapsed or refractory neuroblastoma is associated with a poor outcome. We assessed the combination of irinotecan–temozolomide ...and dasatinib–rapamycin (RIST) in patients with relapsed or refractory neuroblastoma.
The multicentre, open-label, randomised, controlled, phase 2, RIST-rNB-2011 trial recruited from 40 paediatric oncology centres in Germany and Austria. Patients aged 1–25 years with high-risk relapsed (defined as recurrence of all stage IV and MYCN amplification stages, after response to treatment) or refractory (progressive disease during primary treatment) neuroblastoma, with Lansky and Karnofsky performance status at least 50%, were assigned (1:1) to RIST (RIST group) or irinotecan–temozolomide (control group) by block randomisation, stratified by MYCN status. We compared RIST (oral rapamycin loading 3 mg/m2 on day 1, maintenance 1 mg/m2 on days 2–4 and oral dasatinib 2 mg/kg per day for 4 days with 3 days off, followed by intravenous irinotecan 50 mg/m2 per day and oral temozolomide 150 mg/m2 per day for 5 days with 2 days off; one course each of rapamycin–dasatinib and irinotecan–temozolomide for four cycles over 8 weeks, then two courses of rapamycin–dasatinib followed by one course of irinotecan–temozolomide for 12 weeks) with irinotecan–temozolomide alone (with identical dosing as experimental group). The primary endpoint of progression-free survival was analysed in all eligible patients who received at least one course of therapy. The safety population consisted of all patients who received at least one course of therapy and had at least one post-baseline safety assessment. This trial is registered at ClinicalTrials.gov, NCT01467986, and is closed to accrual.
Between Aug 26, 2013, and Sept 21, 2020, 129 patients were randomly assigned to the RIST group (n=63) or control group (n=66). Median age was 5·4 years (IQR 3·7–8·1). 124 patients (78 63% male and 46 37% female) were included in the efficacy analysis. At a median follow-up of 72 months (IQR 31–88), the median progression-free survival was 11 months (95% CI 7–17) in the RIST group and 5 months (2–8) in the control group (hazard ratio 0·62, one-sided 90% CI 0·81; p=0·019). Median progression-free survival in patients with amplified MYCN (n=48) was 6 months (95% CI 4–24) in the RIST group versus 2 months (2–5) in the control group (HR 0·45 95% CI 0·24-0·84, p=0·012); median progression-free survival in patients without amplified MYCN (n=76) was 14 months (95% CI 9–7) in the RIST group versus 8 months (4–15) in the control group (HR 0·84 95% CI 0·51–1·38, p=0·49). The most common grade 3 or worse adverse events were neutropenia (54 81% of 67 patients given RIST vs 49 82% of 60 patients given control), thrombocytopenia (45 67% vs 41 68%), and anaemia (39 58% vs 38 63%). Nine serious treatment-related adverse events were reported (five patients given control and four patients given RIST). There were no treatment-related deaths in the control group and one in the RIST group (multiorgan failure).
RIST-rNB-2011 demonstrated that targeting of MYCN-amplified relapsed or refractory neuroblastoma with a pathway-directed metronomic combination of a multkinase inhibitor and an mTOR inhibitor can improve progression-free survival and overall survival. This exclusive efficacy in MYCN-amplified, relapsed neuroblastoma warrants further investigation in the first-line setting.
Deutsche Krebshilfe.
Abstract
Transcriptional dysregulation has been described in spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD), an autosomal dominant ataxia caused by a polyglutamine expansion in the ...ataxin-3 protein. As ataxin-3 is ubiquitously expressed, transcriptional alterations in blood may reflect early changes that start before clinical onset and might serve as peripheral biomarkers in clinical and research settings. Our goal was to describe enriched pathways and report dysregulated genes, which can track disease onset, severity or progression in carriers of the ATXN3 mutation (pre-ataxic subjects and patients).
Global dysregulation patterns were identified by RNA sequencing of blood samples from 40 carriers of ATXN3 mutation and 20 controls and further compared with transcriptomic data from post-mortem cerebellum samples of MJD patients and controls. Ten genes—ABCA1, CEP72, PTGDS, SAFB2, SFSWAP, CCDC88C, SH2B1, LTBP4, MEG3 and TSPOAP1—whose expression in blood was altered in the pre-ataxic stage and simultaneously, correlated with ataxia severity in the overt disease stage, were analysed by quantitative real-time PCR in blood samples from an independent set of 170 SCA3/MJD subjects and 57 controls.
Pathway enrichment analysis indicated the Gαi signalling and the oestrogen receptor signalling to be similarly affected in blood and cerebellum. SAFB2, SFSWAP and LTBP4 were consistently dysregulated in pre-ataxic subjects compared to controls, displaying a combined discriminatory ability of 79%. In patients, ataxia severity was associated with higher levels of MEG3 and TSPOAP1.
We propose expression levels of SAFB2, SFSWAP and LTBP4 as well as MEG3 and TSPOAP1 as stratification markers of SCA3/MJD progression, deserving further validation in longitudinal studies and in independent cohorts.
Raposo et al. reveal altered Gαi signalling and oestrogen receptor signalling in blood and cerebellum samples from patients with spinocerebellar ataxia type 3/Machado-Joseph disease, and identify five genes whose expression levels could serve as stratification markers for disease progression.
•Our study shows that there is practically no difference between men and women in the productivity measured as the number of articles published.•We base our analysis on matching methods. Using this ...fine-grained analysis we found a much smaller difference between genders with respect to scientific productivity than previous studies.•Furthermore, we found very little (and overall statistically insignificant) difference in the number of received citations between men and women.
The aim of this study is to compare PhD students’ performance with respect to gender using a number of matching methods. The data consists of fine-grained information about PhD-students at the Institute of Clinical Research at the University of Southern Denmark. Men and women are matched controlling for sub-disciplinary affiliation, education, year of enrolment and age. Publications and citations are identified in Web of Science.
Our study shows that the average total number of publication is slightly higher for men than for women. Excluding the “other” group of publications from the analyses reveals that there is a negligible difference between men and women in terms of published articles. A substantial proportion of women is on maternity leave during the time period analysed and thus we would expect their productivity to be considerably lower. Similarly, we have found very little difference between the citation impact of men and women.
We find matching methods to be a promising set of methods for evaluating productivity and impact of individuals from various sub-fields, universities and time periods as we are able to discard some of the underlying factors determining the results of analyses of gender differences in productivity and citation impact.
PDF
